Cancer/testis (CT) antigens constitute a unique group of genes which are predominantly expressed in human germ line cells such as placenta and testis but become reactivated in various malignancies (Simpson et al., Nature Rev (2005) 5, 615-625). Most of these genes are located as multigene families on the X-chromosome and are often referred to as CT-X antigens (Simpson et al., Nature Rev (2005) 5, 615-625). So far their function has not been elucidated; however their involvement in chromosomal recombination, transcription as well as translation and signaling has been proposed (Simpson et al., Nature Rev (2005) 5, 615-625). Analogies have been drawn between their expression pattern during germ maturation and neoplastic transformation, thus suggesting their involvement in several steps of tumorigenesis (Simpson et al., Nature Rev (2005) 5, 615-625).
The expression of CT-X antigens varies greatly between tumor types. While bladder cancer, lung cancer, ovarian cancer, hepatocellular carcinoma and melanoma frequently express CT-X antigens, the abundance of these genes is less frequent in renal cancer, colon, and gastric cancers (Scanlan et al., Cancer Immun (2004) 4, 1). Moreover, their expression pattern is closely associated with advanced disease and poor outcome and might thus be of diagnostic and/or prognostic relevance (Gure et al., Clin Cancer Res (2005) 11, 8055-8062; Velazquez et al., Cancer Immun (2007) 7, 11; Andrade et al., Cancer Immun (2008) 8, 2; Tinguely et al., Cancer Science (2008); Napoletano et al., Am J of Obstet Gyn (2008) 198, 99 e91-97. Due to their highly restricted expression in malignant tissues, their tumor associated peptides provide promising targets for anticancer immunotherapy (Scanlan et al., Immunol Rev (2002) 188, 22-32). Indeed, clinical trials evaluating the role of two CT antigens, namely MAGE-A3 and NY-ESO-1, as targets for specific immunotherapy have already been initiated in a number of different malignancies (Bender et al., Cancer Immunol (2007) 7, 16; Atanackovic et al., PNAS (2008) 105, 1650-1655; Jager et al., PNAS (2006) 103, 14453-14458; van Baren et al., J Clin Oncol (2005) 23, 9008-9021; Valmori et al., PNAS (2007) 104, 8947-8952; Odunsi et al., PNAS (2007) 104, 12837-12842; Davis et al., PNAS (2004) 101, 10697-10702 (9-15).
In breast-cancer most known tumour antigens can be found in normal tissues with elevated and or mutated expression in tumors cells. Some of these antigens such as MUC1, CEA, carbohydrate antigens and HER-2/ERBB2 have already been used to construct vaccines for the treatment of breast cancer (Curigliano et al., Breast (Edinburgh, Scotland) (2007) 16 Supp. 2, S20-26). So far targeted immunotherapy treatment has been successful with the monoclonal antibody trastuzumab (Herceptin®) against HER-2/ERBB2 receptors and it has been shown to be most effective for a subpopulation of breast cancers with HER2/ERBB2 over-expression. While other subtypes such as ER-positive (ER+) breast tumour patients benefit from endocrine and or combinatorial therapy, targeted therapy for a distinctive group of ER-negative (ER−) is still in its infancy. Recent studies have shown good responses for some ER-negative breast cancers with EGFR overexpression when treated with carboplatin in combination monoclonal antibodies (cetuximab) (Hoadley et al., BMC Genomics (2007) 8, 258).
Current clinical management of breast cancer—early detection, surgery and cytotoxic drug regimens often in the adjuvant setting—has resulted in significant gains in disease free and overall survival in recent times (Quinn et al., Br J Cancer (2008) 99 Sup. 1, S53-55). Some additional advances have been achieved through the use of targeted forms of therapy such as Tamoxifen and aromatase inhibitors for those breast cancers possessing estrogen receptors (Herold et al., Clin Breast Cancer (2008) 8, 50-64; Ponzone et al., Ann NY Acad Sciences (2006) 1089, 143-158). Trastuzumab (Herceptin®), a humanized monoclonal antibody against the extracellular domain of HER2, has been shown recently to benefit patients with HER2-positive primary and metastatic disease (Madarnas et al., Cancer Tr Rev (2008) 34, 539-557; Park et al., Ann Oncol (2008)).